E1208 A Phase III Randomized, Double-Blind Trial of Chemoembolization with or without Sorafenib in Unresectable Hepatocellular Carcinoma (HCC) in Patients with and without Vascular Invasion
To compare the progression-free survival of patients with unresectable hepatocellular carcinoma treated with chemoembolization with versus without sorafenib. To compare extra-hepatic versus intra-hepatic patterns of failure and to determine the rates of toxicity related to these regimens in these patients. To determine the inter-reader imaging concordance for response characterization at 4 and 8 months by the European Association for the Study of Liver (EASL) criteria.
18 Years and older.Histologically confirmed disease.Disease must be limited to the liver. No clinical or radiographic evidence of extrahepatic HCC. Child Pugh score of A or B7 within the past 4 weeks. No ascites detectable on physical evaluation. Not a candidate for curative resection, orthotopic liver transplantation, or radiofrequency ablation (RFA). ECOG performance status 0-1. Life expectancy more than 3 months. Not pregnant or nursing. Negative pregnancy test. Fertile patients must use effective contraception. Able to swallow pills. No clinical signs of heart failure. No NYHA class III or IV heart disease. No evidence of bleeding diathesis or active gastrointestinal bleeding. No known HIV positivity . No other concurrent uncontrolled illness (except hepatitis B or C) including, but not limited to, any of the following:Uncontrolled hypertension (i.e., optimally treated baseline BP greater than 150/90 mm Hg), Symptomatic congestive heart failure, Unstable angina pectoris,Cardiac arrhythmia,Psychiatric illness and/or addictive disorder that would limit compliance with study requirements.No concurrent cytochrome P450 enzyme-inducing drugs.No concurrent prophylactic G-CSF or GM-CSF.
Arm I: Patients receive oral sorafenib twice daily in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of sorafenib is reached, patients undergo transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride, mitomycin C, and cisplatin; conventional chemoembolization comprising doxorubicin hydrochloride only; or chemoembolization comprising doxorubicin-eluting beads. Treatment with TACE repeats approximately every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral placebo twice daily in the absence of disease progression or unacceptable toxicity. Beginning within 2 weeks after a stable dose of placebo is reached, patients undergo TACE as in arm I.
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